Endocytosis is a critical cellular process for the internalization of nanoparticles (NPs), which play a very important role in clinical and biomedical applications such as targeted drug delivery, gene therapy, and diagnostics. In this review, a comprehensive comparison is made between the endocytosis mechanisms of two types of nanoparticles widely used in many applications: the first is mesoporous silica nanoparticles (MSNs), and the second one is silver nanoparticles (AgNPs). MSNs have the characteristics of high surface area, tunability of the surface properties, and are also safe and tissue compatible, making them suitable for targeted drug delivery. The primary endocytosis mechanism by receptor-mediated endocytosis, as clathrin- and caveolae-mediated pathways. On the other hand, AgNPs, known for their antibacterial and antimalignant properties, are, through a combination of clathrin-mediated endocytosis and macropinocytosis. With clear therapeutic potential, AgNPs show cytotoxicity due to silver ion release and (ROS) generation of reactive oxygen species. This review highlights how particle shape, size, surface charge, and surface functionalization affect the uptake mechanisms and intracellular fate of these NPs. Also, the impact of NPs properties on toxicity, interaction, and targeted drug delivery efficiency is clarified. Understanding those factors is important for optimizing NPs design and supporting their applications in diagnostics and nanomedicine. The review comparison show that MSNs have superior properties for drug delivery and low toxicity levels while the AgNPs have potent effect in cancer therapeutics and antimicrobial use.